1,3,5-triazines for treatment of viral diseases

Abstract

The present invention provides compounds and methods for treatment of viral diseases and cancer.

1. A method for treating Human Immuno-Deficiency Virus (HIV) comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound having the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 R 9  and R 10  are members independently selected from H, substituted or unsubstituted alkyl and acyl; 
 R 3  is H; 
 R 4  is H; 
 R 5  is OR 14 , wherein R 14  is a member selected from H and unsubstituted alkyl; 
 R 6  is OR 14 , wherein R 14  is a member selected from H, substituted or unsubstituted alkyl and P(O)(OR 17 )(OR 17 ), wherein each R 17  is independently selected from H, substituted alkyl, substituted or unsubstituted alkyloxy and substituted or unsubstituted phenyl; and 
 R 8  is selected from H and unsubstituted alkyl. 
 
     
     
       2. The method of  claim 1 , wherein said compound is given orally. 
     
     
       3. The method of  claim 2 , wherein said compound is an enteric formulation. 
     
     
       4. The method of  claim 3 , wherein said compound is delivered in an oral osmotic drug delivery device. 
     
     
       5. The method of  claim 1 , wherein the HIV is resistant to nucleotide reverse transcriptase inhibitors. 
     
     
       6. The method of  claim 1 , comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       7. The method of  claim 1 , comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       8. The method of  claim 1 , wherein R 6  has the formula: 
       
         
           
           
               
               
           
         
         in which 
         R 22  is a member selected from substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl; 
         L is a linker selected from substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl; and 
         Ar is a substituted or unsubstituted aryl. 
       
     
     
       9. The method of  claim 8 , wherein L comprises a moiety that is cleaved in vivo after entry of said compound into a cell. 
     
     
       10. The method of  claim 1 , wherein R 6  has the formula: 
       
         
           
           
               
               
           
         
         in which 
         R 22  is a member selected from substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl; 
         L is a linker selected from substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl; and 
         n is an integer from 1 to 30. 
       
     
     
       11. The method of  claim 10 , wherein L comprises a moiety that is cleaved in vivo after entry of said compound into a cell. 
     
     
       12. The method of  claim 1 , wherein the compound is administered in combination with another antiviral drug. 
     
     
       13. The method of  claim 12 , wherein the antiviral drug is a member selected from the group consisting of acyclovir, amantadine azidothymidine (AZT or Zidovudine), ribavirin, amantadine, vidarabine and vidarabine monohydrate (adenine arabinoside, ara-A). 
     
     
       14. The method of  claim 1 , wherein the compound has the formula: